Article pubs.acs.org/JPCB
Interaction of a Julolidine-Based Neutral Ultrafast Molecular Rotor with Natural DNA: Spectroscopic and Molecular Docking Studies Rahul Kalel,†,‡ Aruna K. Mora,† Rajib Ghosh,† Dilip D. Dhavale,‡ Dipak K. Palit,† and Sukhendu Nath*,† †
Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India Department of Chemistry, Savitribai Phule Pune University, Pune 411007, India
‡
S Supporting Information *
ABSTRACT: Ultrafast molecular rotors (UMRs) are reported to be one of the best fluorescent sensors to study different microenvironments, including biomolecules. In the present work, we have explored the possibility of application of a julolidine-based neutral UMR, 9-(2,2-dicyano vinyl) julolidine (DCVJ), as a DNA sensor and studied its mode of binding with DNA in detail using spectroscopic and molecular docking techniques. Our spectroscopic studies indicate that association of DCVJ with DNA leads to a very large enhancement in its emission intensity. Detailed investigation reveals that, despite being a neutral molecule, binding of DCVJ with DNA is largely modulated in the presence of salt. Such an unusual salt effect has been explained by invoking the ion−dipole interaction between DCVJ and the phosphate backbone of DNA. The ion−dipole interaction has also been established by studying the interaction of DCVJ with nucleosides. Detailed timeresolved studies show that the twisting motion around the vinyl bond in DCVJ gets retarded to a great extent because of its association with DNA molecules. Through competitive binding studies, it has also been established that DCVJ also binds to DNA through intercalation. Finally, quantum chemical calculations and molecular docking studies have been performed to confirm the mode of binding of DCVJ with DNA. environments, indicating their potential as a fluorescence sensor for different complex environments. It is to be noted that unlike other fluorescence sensors mentioned earlier fluorescence enhancement of a UMR is purely due to physical confinement and barely depends on its relative orientation with respect to the confined media. In recent years, such a UMR has been used to characterize different complex environments, such as macrocyclic host molecules,25−27 cross-linked polymers,28,29 and biomolecules.30,31 Recently, we have shown that one of the benzothiazole-based UMRs is much more efficient in detecting DNA as compared to most commonly used DNA stains.31 It was further demonstrated that such UMRs can probe small changes in the secondary structure of DNA, which could not be detected by any other techniques including circular dichroism spectroscopy. 9-(2,2-Dicyano vinyl) julolidine (DCVJ) (see Scheme 1 for molecular structure), a UMR, has a very low emission yield (∼10−4) in low-viscosity solvents.32,33 Allen et al. have shown that in the ground state the dihedral angle between the vinyl and julolidine groups is only 8°, indicating the planarity of the molecule.33 However, in the excited state, twisting around the vinyl bond leads to an orthogonal orientation between vinyl and julolidine moieties. Such bond-twisting is a barrierless process and hence very fast and efficient. Further, the twisted
1. INTRODUCTION Quantification of DNA, the primary cellular data storing device, is very crucial for pathological evaluation of biological samples. Extensive research has been carried out to develop a simple yet sensitive method for the detection of DNA.1−6 Among these methods, detection of DNA using fluorescence-based techniques has attracted the most attention due to its simplicity and remarkable sensitivity. Fluorescent DNA sensors are primarily based on the principle of energy transfer,7−9 electron transfer,10−13 H-bonding interaction,14−17 π−π stacking,18−21 and so forth. The efficiency of such sensors largely depends on the relative orientation between the small sensor molecule and nucleic acid bases. For example, the efficiency of a sensor based on the energy transfer principle largely depends on the distance between the donor and acceptor moieties and their relative orientation. Furthermore, the efficiency is also largely determined by the extent of overlap between the emission spectrum of donor and the absorption spectrum of acceptor moieties. Because of these factors, only limited efficiency for such sensors has been achieved so far. Ultrafast molecular rotors (UMRs) are a class of molecules that undergo ultrafast twisting motion in their excited states to produce nonemissive twisted states and lead to extremely low emission yields (
